Thursday, August 02, 2007

Drug induced QT interval prolongation

This topic was reviewed in a recent issue of American Heart Journal. QT prolongation and associated torsade de pointes (TdP) are the most common reasons for drug restriction in the U.S. market. Although the advent of preclinical molecular testing during drug development lessens the likelihood of new arrhythmogenic drugs unexpectedly entering the U.S. market the list of drugs causing QT prolongation and TdP continues to grow, with the most notable recent addition being an old medication, long believed to be safe, which is methadone.

The review discusses electrophysiologic mechanisms, guidelines for QT interval measurement and QTc determination and points the reader to web resources on drugs which prolong the QT interval, all of which I have previously provided here.

Most patients who develop drug induced TdP have at least one additional risk factor, including female sex, interacting drugs, electrolyte disturbances and genetic polymorphisms. This latter risk factor raises the issue of interaction between genetic susceptibility and drug effects with some patients having a forme fruste of congenital LQTS.